P979: PATIENT-REPORTED OUTCOMES FOR TECLISTAMAB VERSUS REAL-WORLD PHYSICIAN’S CHOICE OF THERAPY IN THE LOCOMMOTION STUDY IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: Philippe Moreau, Niels W.C.J. van de Donk, Michel Delforge, Hermann Einsele, Valerio De Stefano, Aurore Perrot, Britta Besemer, Charlotte Pawlyn, Lionel Karlin, Salomon Manier, Xavier Leleu, Pushpike Thilakarathne, Joris Diels, Katharine Gries, Nichola Erler-Yates, Kirsten van Nimwegen, Raúl Morano, Vadim Strulev, Imene Haddad, Rachel Kobos, Jennifer Smit, Alexander Marshall, Mary Slavcev, Maria-Victoria Mateos, Katja Weisel
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Indirect treatment comparisons between the phase 1/2 MajesTEC-1 study (NCT04557098) and real-world (RW) studies have shown improved effectiveness with teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, over RW physician's choice (RWPC) of therapy in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM) who had received ≥3 prior lines of therapy (Krishnan et al, IMS 2022, P-251; Mateos et al, IMS 2022, P-281; van de Donk et al, IMS 2022, OAB-054). Here, we present patient-reported outcomes (PROs) for teclistamab in MajesTEC-1 vs those for RWPC in the prospective, noninterventional LocoMMotion study (NCT04035226). Aims: To report a comparative analysis of PROs from the MajesTEC-1 and LocoMMotion studies. Methods: PROs from the phase 2 portion of MajesTEC-1 (N=125, enrolled Oct 2020–Aug 2021; clinical cut-off, Mar 16, 2022) were compared with an external control arm of patients from LocoMMotion (N=248, enrolled Aug 2019–Oct 2020; clinical cut-off, Nov 2, 2021). All patients provided informed consent. PROs were assessed at baseline and on day 1 of every other treatment cycle (up to cycle 16) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EuroQol Five Dimension Five Level (EQ-5D-5L) questionnaires. Differences in changes from baseline (CFB) between both treatment cohorts were estimated for each PRO domain using a mixed model of repeated measures (MMRM), including baseline prognostic variables as covariates to adjust for confounding bias. MMRM analyses included patients with baseline and post-baseline PRO assessments (teclistamab, n=85; RWPC, n=170). PRO assessment was limited after disease progression; the MMRM approach does not account for the selective dropout of patients who progressed or died, which may underestimate the PRO benefit of teclistamab due to its longer progression-free survival and overall survival vs RWPC. To correct for this inherent survival bias, a responder analysis was performed for each PRO domain, estimating the percentage of patients who were progression-free with clinically meaningful changes in outcomes, defined by a threshold of ≥10 points on a 1–100 scale, over time. Results: Estimates for mean differences in CFB were significantly in favor of teclistamab over RWPC (P<0.05) for several PRO domains, including the EQ-5D-5L visual analogue score (VAS; 4.5), the EORTC QLQ-C30 global health score (GHS; 6.5), emotional functioning (7.4), pain (–6.2), and dyspnea (–9.5) (Table). There were no domains that significantly improved in favor of RWPC over teclistamab. At 9 months, responder analyses showed significantly more patients with clinically meaningful improvement for teclistamab over RWPC for VAS (27.5% vs 6.4%); GHS (24.1% vs 10.3%); functional PROs, including physical (17.2% vs 10.3%), role (25.9% vs 10.3%), social (22.4% vs 9.0%), cognitive (10.3% vs 5.1%), and emotional (27.6% vs 3.9%); and symptom PROs, including nausea and vomiting (10.3% vs 3.9%), diarrhea (17.2% vs 5.1%), appetite loss (12.1% vs 1.3%), and insomnia (15.5% vs 7.7%) (all P<0.05). Summary/Conclusion: Teclistamab showed significantly improved PROs over RWPC in patients with triple-class exposed RRMM. This highlights the positive impact teclistamab can have on health-related quality of life in addition to significant efficacy benefits to help address the high unmet need for this patient population.Keywords: Real world data, Patient reported outcomes, Multiple myeloma, Clinical trial